Blood vessels in humans and animals are grouped as arterial and venous, determined by whether the blood in it is flowing away from (arterial) or toward (venous) the heart.
Caused by lack of activity, an increasing number of people show venous congestion. If no change in habits occurs, congestion turns into insufficiency within few years. Insufficiency means that vein valves become incompetent, resulting in a reversed blood flow. In a vicious circle insufficiency further increases venous blood congestion, and the disease increases with time. Varicose veins are superficial veins which have been stressed by an overload of blood for years and therefore show large diameters and a tortuous course. Incompetent veins are found in 21-25% of people aged 35 or above, and spider veins even in 50% (Uldis Maurins, Barbara H. Hoffmann, Christian Liisch, Karl-Heinz jockel, Eberhard Rabe, Felicitas Pannier: Distribution and prevalence of reflux in the superficial and deep venous system in the general population—results from the Bonn Vein Study, Germany. Journal of Vascular Surgery, Vol 48, Issue 3, September 2008, 680-687)
Beside the cosmetic issues, insufficient and varicose veins lead to major complications, due to the congestion and the poor circulation through the affected limb. The complications comprise pain, heaviness, inability to walk or stand for long hours, skin inflammation, skin damage predisposing skin loss or skin ulcers especially near the ankle, usually referred to as venous ulcers, severe bleeding from minor trauma, blood clotting within affected veins (thrombophlebitis, thrombosis, embolic events). Even the development of carcinoma or sarcoma in longstanding venous ulcers has been reported in over 100 cases. The rate of malignant transformation is reported as 0.4% to 1% (Goldman M. Sclerotherapy, Treatment of Varicose and Telangiectatic Leg Veins. Hardcover Text, 2nd Ed, 1995).
For dilated veins, surgical removal of the target structure, e.g. varicose veins, is a widely used therapy. However, like all surgical treatments this may be accompanied by several, partially serious adverse effects, i.e. damaging of adjacent arteries, nerves or lymphatic vessels, generation of wounds and cicatrices, wound infections, or intolerance of the patient for narcotic drugs.
As an alternative to surgical removal, different ways of sclerotherapy have been developed.
The aim of a sclerotherapy is the permanent closure of the treated vein or vein segment. The effect may be obtained by endovascular thermal treatment (e.g. by laser, radiofrequency, steam), or by injection of chemical agents (fluids, foams). Due to the use of catheters and probes, thermal treatment is restricted to relatively linear vessels while chemical agents may also reach curved segments.
The effect of all these methods is to denature functional proteins in the innermost tissue layer (the endothelial cell layer). Effects may even reach the muscle layer of the vein. Said denaturing process triggers a shrinking of the tissue resulting in the occlusion of the target structure. Only parts of the vessel wall sufficiently reached by the sclerotic agent can be expected to close permanently, as undamaged endothelium will revitalize and lead to recurrent pathologic blood flow.
All sclerotherapy procedures are more or less associated with a local vein spasm, due to effects on the muscular layer. The spasm in general is not lasting longer than minutes above the activity of the modality, although it would be desirable to maintain it in the aim to normalize the vessel diameter. A real initial shrinking can only be obtained if the effect reaches deep into the muscular layer. On the other hand, with increasing effects on the muscular layer the danger of perforation increases, and so does pain during and after treatment.
Known liquid sclerosant drugs are e.g. alcohols with detergent properties like polidocanol or sodium tetradecyl sulphate. The liquid sclerosant drug is injected into the vessels. Due to its high fluidity the liquid sclerosant drug flows with the blood stream and quickly mixes with blood, soon reaching ineffective dilutions. Protein bindings additionally limit the effect of these fluid agents.
In order to circumvent some drawbacks of the liquid sclerosant drugs, it has been established to produce a sclerosant drug foam by mixing the liquid sclerosant drug with a gas. The resulting sclerosant drug foam is injected into the target structure, e.g. the varicose vein. For foaming the sclerosant drug (e.g. Sodium Tetradecyl Sulfate or polidocanol) is mixed with sterile air or a physiological gas (carbon dioxide) in a syringe or by using mechanical pumps.
Foaming increases the surface area of the drug. Due its higher stiffness and viscosity, the sclerosant drug foam is more efficacious in causing sclerosis than the liquid sclerosant drug (thickening of the vessel wall and sealing off the blood flow; Yamaki T, Nozaki M, Iwasaka S (2004). “Comparative study of duplex-guided foam sclerotherapy and duplex-guided liquid sclerotherapy for the treatment of superficial venous insufficiency”, Dermatol Surg 30 (5): 718-22) for it does not mix with the blood in the vessel and in fact displaces it. However, sclerosant drug foams of prior art are still disintegrated rapidly within vessels. The sclerosant drug is therefore washed away from the target structure. Hence, sclerosant drug foams of prior art are not well suited for treatment of larger target structures, as they only cause painful inflammatory reactions without long lasting achievements with respect to the occlusion of the target structures. Furthermore, the sclerosant drug foams of prior art have a significant lower density than blood. This results in floating of the sclerosant drug foam on the blood within the vessels. Hence, the sclerosant drug often does not reach all portions of the vessel within the target structure.
Once a vessel disease has been treated as outlined above, the vascular dilatation or aneurysm may remain as a space consuming structure. Pressure on the neighboring nerves, vessels or organs may still remain although the diseased vessel is occluded. The larger the diameter of the diseased vein, the higher is the risk of a relapse.
For obliteration treatment of enlarged vessels, in particular sclerosant drug foam treatment, it would be advantageous to have a substance that may be used by means of injection around the dilated or aneurysmatic vessel in order to restrict its diameter. Most substances like saline solutions have turned out to be too transient. It would also be advantageous to have a substance to compress dilated veins (or vein valve zones) for a time of days to several weeks until relaxation has restored the vein function.
Thus, the present invention solves the problem by providing an aqueous solution comprising between 0.1% and 3% hyaluronic acid, and an injection kit for paravascular application.
WO 2011/037912 relates to enhancing tissue repair. It makes use of glycosaminoglycan for platelet activation, i.e. tissue repair.